Aripiprazole having the structure shown in the following Formula 1 is, an atypical anti-psychotic and antidepressant drug, and exhibits a potent affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors; a mild affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, α1-adrenaline agonist and histamine H1 receptors; and a mild affinity for serotonin reuptake sites.

Aripiprazole has no detectable affinity for cholinergic muscarinic receptors. Similarly to other drugs having an efficacy against schizophrenia, the mechanism of action of aripiprazole has not been identified. However, it has been proposed that the efficacy of aripiprazole is mediated through the combination of an activity for partial acceleration at the D2 and 5-HT1A receptors (agonist) and an activity for antagonism at the 5-HT2A receptors (antagonist).
U.S. Pat. No. 5,006,528 and Japanese Early Published Patent No. 02-191256 disclose that the crystal of anhydrous aripiprazole can be prepared either by recrystallizing anhydrous aripiprazole from ethanol or by heating aripiprazole hydrate at a temperature of 80° C.
Further, in a bulletin of the Fourth Japan-Korea Symposium for Separation Techniques (Oct. 6-8, 1996), it was disclosed that anhydrous aripiprazole can be present in the crystal forms I and II.
Aripiprazole crystal form I can be prepared by recrystallizing aripiprazole from ethanol solution or by heating aripiprazole hydrate at a temperature of 80° C. However, anhydrous aripiprazole crystal form I obtained from such a method is disadvantageous in view of the fact that it has a significant hygroscopic property. Thus, upon exposure to moisture the anhydrous crystal form I can absorb the moisture and be converted into the hydrate form, and is thus inferior to the anhydrous crystal form II in view of bioavailability and resolvability.
Aripiprazole crystal form II can be prepared by heating the hydrate of aripiprazole crystal form I at a temperature of 130 to 140° C. for 15 hours (see the bulletin of the Fourth Japan-Korea Symposium). However, this method cannot be readily applied to industrial scale production of anhydrous aripiprazole, due to the disadvantages involved in long working time at a high temperature.
WO 07/041414 discloses that aripiprazole crystal form II can be prepared by seeding aripiprazole crystal form II into acetone solvent containing the starting aripiprazole such as compound 1, compound 2, crystal form I, crystal form II, crystal form VI, crystal form VIII, crystal form X, crystal form XXI, etc., and then slurrifying the mixture at 30° C. to 50° C. for 2 to 22 hours. However, this method is also not suitable for industrialization due to the problems involved in slurrification under a warming condition for a long period of time.